Volume 31, Number 3—March 2025
Research
Effect of Prior Influenza A(H1N1)pdm09 Virus Infection on Pathogenesis and Transmission of Human Influenza A(H5N1) Clade 2.3.4.4b Virus in Ferret Model
, Jessica A. Belser, Zhu-Nan Li, Nicole Brock, Joanna A. Pulit-Penaloza, Troy J. Kieran, Claudia Pappas, Hui Zeng, Jessie C. Chang, Paul J. Carney, Brandon L. Bradley-Ferrell, James Stevens, Terrence M. Tumpey, Min Z. Levine, and Taronna R. Maines
Table
Pathogenicity and transmissibility of influenza viruses in naive and preimmune ferrets in study of the effect of prior influenza A(H1N1)pdm09 virus infection on pathogenesis of human influenza A(H5N1) clade 2.3.4.4b virus in ferret model*
| Challenge virus | Inoculated animals‡ |
Contact animals |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Status† |
Dose, PFU§ | Lethargy¶ | Temp. rise, °C# | % Weight loss** | Peak titer (SD)†† | Peak titer (SD)†† | Transmission/ inoculation‡‡ | ||||
| Donor | Contact | ||||||||||
| Texas/37 | Naive | Naive | 100.5 | 1.5 | 2.4 (2/2) | 7.3 (2/2) | 5.5 (0.7) | 2.5 (0.6) | 2/2 | ||
| Texas/37 | Naive | Preimmune | 102.4 | 1.9 | 1.7 (3/3) | 7.9 (3/3) | 4.2 (0.4) | NA | 0/3 | ||
| Texas/37 | Preimmune | Naive | 102.4–2.5 | 1.7 | 1.5 (2/3) | 5.5 (2/3) | 2.5 (1.8) | NA | 0/3 | ||
| Anhui/1 | Naive | Naive | 102.7 | 1.2 | 1.9 (2/3) | 4.7 (3/3) | 5.7 (0.8) | 6.1 (1.5) | 3/3 | ||
| Anhui/1 | Naive | Preimmune | 102.8 | 1.1 | 1.5 (2/3) | 5.4 (1/3) | 6.5 (0.4) | 5.4 (0.8) | 3/3 | ||
| Anhui/1 | Preimmune | Naive | 102.6 | 1.1 | 1.6 (2/3) | 5.4 (2/3) | 6.3 (0.2) | 3.3 (1.5) | 2/3 | ||
*Preimmune ferrets were those inoculated with influenza A(H1N1)pdm09 (A/Nebraska/14/2019). Naive and preimmune ferrets were challenged with highly pathogenic influenza A(H5N1) clade 2.3.4.4b A/Texas/37/2024 (Texas/37) and low pathogenicity influenza A(H7N9) A/Anhui/1/2013 (Anhui/1). NA, not applicable because titers were below the limit of detection; temp., temperature. †Ferrets were serologically naive to contemporary influenza A viruses (naive) or inoculated with A/Nebraska/14/2019 influenza A(H1N1)pdm09 virus 3 months before use in this study (preimmune). ‡Inoculated ferrets were monitored for clinical signs of disease for 3 days for the Texas/37 virus and 4 days for the Anhui/1 virus. All animals that were productively infected after aerosol exposure are shown (n = 3 for all groups except Texas/37 naive donor/naive contact, which is n = 2). §Presented dose of virus to ferrets following 15-min inhalation exposure to aerosolized virus. ¶Relative inactivity index of ferrets inoculated with the challenge virus specified. #Values in parentheses are no. affected/no. inoculated. Mean maximum temperature rise >1°C among all inoculated animals in degrees centigrade; number of ferrets with temperature rise >1°C in all productively infected ferrets was shown in parentheses. **Values in parentheses are no. affected/no. inoculated. Mean maximum weight loss >1% among all inoculated animals expressed as a percentage; number of ferrets with weight loss >1% in all productively infected ferrets was shown in parentheses. ††Mean maximum nasal wash titer +SD reported as log10 PFU/mL among ferrets with positive virus shedding; for NA, titers for all ferrets were below limit of detection of 10 PFU. ‡‡Values are no. affected/no. inoculated. Transmission was defined as both the detection of productive virus shedding and seroconversion of surviving animals to homologous challenge virus or confirmed infection requiring euthanasia. Two contact ferrets, each co-housed with a ferret productively infected with the Texas/37 virus, were humanely euthanized on days 3 and 4 postcontact; all contact ferrets co-housed with ferrets inoculated with Anhui/1 virus survived through day 21 postcontact.